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SAT0213 Low dose il-2 restores decreased absolute number of regulatory t cells and imbalance between th17 and regulatory t cells in patients with rheumatoid arthritis
  1. R Jia1,
  2. X Li1,
  3. C Wang1,
  4. C Gao2
  1. 1The Department of Rheumatology, the Second Hospital of Shanxi Medical University, Taiyuan, China
  2. 2Pathology, Joint Program in Transfusion Medicine, Brigham and Women's Hospital/Children's Hospital Boston, Harvard Medical School, Boston, United States

Abstract

Background A therapeutic revolution in the past decade is still a considerable unmet need in the treatment of rheumatoid arthritis (RA). On the other hand, dysfunction of regulatory T cells (Tregs) has been considered to be a pivotal cause of RA and correction of this dysfunction to be a potential RA therapy1. However, abnormalities of Tregs in patients with RA were reported controversially in previous studies2, in which only proportion was measured and Tregs were defined using different protein markers.

Objectives In this study, we measured both absolute numbers and proportions of CD4+CD25+Foxp3+ Tregs in peripheral blood of RA patients and investigated the effects of low-dose recombinant human IL-2 (rhIL-2) on Tregs and CD4+ effector T cell subsets in patients with RA.

Methods Both absolute numbers and proportions of Treg and Th17 cells in peripheral blood, defined as the CD4+CD25+FOXp3+T or CD4+IL-17 + T cell population, were examined by flow cytometry in 342 patients with RA with different 28-joint Disease Activities (DAS28), including 75 who had never received disease-modifying antirheumatic drugs (DMARD) and 151 who were receiving or had received DMARD. Among these patients, 112 consented at enrollment to receive rhIL-2 treatment. Before and after treatment, the Th17 and Treg cells in peripheral blood were analyzed by flow cytometry.

Results The absolute count of Treg cells in patients with RA was significantly low compared with that of healthy controls (P<0.05), but the absolute count of Th17 cell was no different between RA and healthy controls. After the course of rhIL-2 treatment, there was a significant increase in the absolute count of Th17 and Treg cells in the CD4+ T cell population (P<0.01), but Th17/Treg was significantly low after the treatment.

Conclusions The data suggest that, besides propotion, the decrease of Treg cell number, defined as the CD4+CD25+FOXp3+population, may contribute to the pathogenesis of RA. Over the treatment of rhIL-2, there was a more significant increase in the absolute count of Treg cells than that of Th17, and consequently restore the balance of Th17/Treg.

References

  1. Miyara M, Ito Y, Sakaguchi S. TREG-cell therapies for autoimmune rheumatic diseases. Nature reviews Rheumatology 2014;10:543–51.

  2. Morita T, Shima Y, Wing JB, Sakaguchi S, Ogata A, Kumanogoh A. The Proportion of Regulatory T Cells in Patients with Rheumatoid Arthritis: A Meta-Analysis. PloS one 2016;11:e0162306.

References

Disclosure of Interest None declared

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